Intermediate aggregates resulting in the interaction of bile salt with liposomes studied by transmission electron microscopy and light scattering techniques

The interaction of sodium cholate (SC) with phosphatidylcholine liposomes was studied by means of transmission electron microscopy (TEM), changes in the mean particle size (quasielastic light scattering, QELS) and in the static light scattering (SLS) of the system during liposome solubilization. A good correlation was found between the TEM diameter of particles and the mean hydrodynamic diameter (HD) determined by QELS. The intermediate aggregates resulting in this interaction were dependent on the SC concentration in the system. Thus, an initial vesicle growth occurred when the SC concentration in the system was 13.79 mol%. Additional SC amounts (41.17 mol% SC) led to the formation of the largest vesicles (HD 410 nm). Increasing SC amounts led to a slight fall in the vesicle diameter and in the SLS of the system. Thus, for 47.08 mol% SC, TEM images still showed the presence of vesicles albeit with traces of smaller structures and signs of vesicle fusion. When SC concentration exceeded 48 mol% an abrupt decrease in SLS occurred, the size curve starting to show a bimodal distribution. Thus, for 50 mol% SC a sharp distribution curve appeared at 52 nm indicating the formation of small particles and TEM images showed clear signs of vesicle disintegration with formation of tubular structures. The subsequent self organization of these tubular structures (54 mol% SC) led to the formation of open multilayered structures in coexistence with small particles. A gradual increase in the number of these small particles (mixed micelles) led to the complete solubilization of liposomes.